GENOMIC ANALYSIS OF BREAST CANCER GERMLINE GENETIC VARIANTS FROM THE QATAR GENOME PROJECT

Abstract

Breast cancer (BC) remains a worldwide health concern, affecting more than 2.3 million females globally. The huge advancements in the next generation sequencing (NGS) technologies have encouraged many countries to launch population genome projects for better personalized medicine. By leveraging whole genome sequencing (WGS) data from Qatar Genome Project (QGP), we profiled the genomic landscape of Qatari population with confirmed breast cancer diagnosis. In this study, we analyzed germline variants from 22 breast cancer predisposition genes, which are known to be highly associated with familial BC progression. By comprehensively characterizing those genes, a lower frequency of pathogenic variants was detected in the Qatari population compared to Middle Eastern population. In addition, we identified pathogenic SNPs and InDels in BRCA1 (rs80187739, rs397509141) and CHEK2 (rs730881701) genes. Compared with other populations, the variants occur at low frequency worldwide, with a putative founder mutation specific to individuals from the Middle East. Furthermore, we analyzed the variants with unknown (VUS) and found a potentially novel pathogenic variant in the STK11 gene in the Qatari cohort. The findings from this study represent an important step toward characterizing the hereditary BC in Qatar and for precision medicine implementation, and also contribute to broader knowledge about germline genetics in Arab populations.